SCN1B Gene: A Close Relative to SCN1A

2021 ◽  
Author(s):  
Elisa Pasquetti ◽  
Manuela Lo Bianco ◽  
Federica Sullo ◽  
Francesca Patanè ◽  
Laura Sciuto ◽  
...  
Keyword(s):  
Gene Mutations ◽  
Febrile Seizures ◽  
Dravet Syndrome ◽  
Close Relative ◽  
Epilepsy Syndrome ◽  
Neuronal Function ◽  
Excitable Cells ◽  
Epileptic Encephalopathies ◽  
Generalized Epilepsy ◽  
Febrile Seizures Plus

AbstractOne of the first reported genes associated with epilepsy was SCN1B, which encodes for β-subunit of voltage-gated sodium channel of excitable cells and it is critical for neuronal function in both central and peripheral nervous system. β-subunits modulate the expression levels and functional properties of sodium channels and though their immunoglobulin domains may mediate interactions between channels and other proteins. Traditionally, SCN1B mutations were associated with generalized epilepsy with febrile seizures plus, a familial epilepsy syndrome characterized by heterogeneous phenotypes including febrile seizures (FS), febrile seizures plus (FS + ), mild generalized epilepsies, and severe epileptic encephalopathies. Throughout the years, SCN1B mutations have been also associated with Dravet syndrome and, more recently, with developmental and epileptic encephalopathies, expanding the spectrum associated with this gene mutations to more severe phenotypes.

Severe Epilepsy Syndromes of Early Childhood: The Link Between Genetics and Pathophysiology With a Focus on SCN1A Mutations

2009 ◽  
Vol 24 (8_suppl) ◽  
pp. 15S-23S ◽  
Author(s):  
Carl E. Stafstrom
Keyword(s):  
Early Childhood ◽  
Sodium Channel ◽  
Gene Mutations ◽  
Febrile Seizures ◽  
Dravet Syndrome ◽  
Epilepsy Syndrome ◽  
Accessory Subunits ◽  
Epilepsy Gene ◽  
Generalized Epilepsy ◽  
Severe Epilepsy

Advances in genetics have increased our understanding of the underlying pathophysiologic mechanisms that cause severe epilepsy syndromes of early childhood. Many of the mutations associated with these syndromes are located in genes coding for ion channels or their accessory subunits, giving rise to the concept of epilepsy ``channelopathies.'' In particular, the SCN1A gene coding for the pore-forming a-subunit of the voltage-gated sodium channel NaV1.1 appears to be a common target for epilepsy syndrome-specific mutations. An SCN1A mutation can potentially result in either a gain or loss of sodium channel function. Epilepsies linked to SCN1A mutations range from a relatively benign syndrome called generalized epilepsy with febrile seizures plus to severe childhood epilepsies such as severe myoclonic epilepsy of infancy (Dravet syndrome). The availability of genetic tests for SCN1A mutations is expanding awareness of the spectrum of diseases mediated by this gene and is beginning to permit genotype— phenotype correlations. Eventually, such information might enable clinicians to select an appropriate therapeutic regimen for patients with specific epilepsy gene mutations.

scholarly journals Sodium channels of SCNIA gene mutations in generalized epilepsy with febrile seizure plus (GEFS+) spectrum related to autism

2010 ◽  
Vol 50 (3) ◽  
pp. 125
Author(s):  
Elisabeth Herini ◽  
Yudha Patria ◽  
Gunadi Gunadi ◽  
Surini Yusoff ◽  
Indra SAri Kusuma Harahap ◽  
...  
Keyword(s):  
Gene Mutations ◽  
Febrile Seizures ◽  
Chromatography Analysis ◽  
Indonesian Population ◽  
A Subunit ◽  
Dsm Iv ◽  
Generalized Epilepsy ◽  
Febrile Seizures Plus ◽  
Intron 4 ◽  
Intron 2

Background Mutations in the a-subunit of the first neuronalsodium channel gene SCNIA have been demonstrated forgeneralized epilepsy \\lith febrile seizures plus (GEFS+), severemyoclonic epilepsy in infancy (SMEI), and borderline SMEI(SMEB). SCNIA mutations are also described in patients 'Withpsychiatric disorders such as autism.Objective To identify the mutations of SCNIA gene in patientswith GEFS+ spectrum which may be related to autism.Methods We examined four patients v.ith autism and GEFS+spectrum who were admitted to the Department of Child Health,Sardjito Hospital, Yogyakarta, Indonesia. Diagnosis of autism wasbased on DSM􀁟IV;ICD X criteria. Mutations in SCNIA wereidentified by PCRamplification and denaturing high􀁟performanceliquid chromatography analysis, Mth subsequent sequencing.Results There were four patients, all boys, aged 1.8 year to 7 years.The phenotypes of epilepsy were GEFS+ in one patient, SMEBin one patient and SMEI in two patients. Sequencing analysisrevealed a G􀁟to􀁟A heterozygous transition which was detectedat nucleotide c.4834G>A (p.V1612I ) in exon 25. Other singlenucleotid polymorphisms (SNPs) were c.383 +66T>C in intron 2,c.603-91G>A and c.603-1060> T in intron 4, c.965-21C> T inintron 6, c.1028+21T>Cin intron 7, c.2173G>A in exon 12 andc. 2177-38C>A, c.2177-12delT, c.2176+44C> T in intron 12.Conclusion In this study, we reported the first cases Mth mutationin SCNIA gene in GEFS+ spectrum related to autistic patientsin Indonesian population, which showed a missense mutationp.V16121. [Paediatr lndones. 2010;50:125-32].

Dravet syndrome or genetic (generalized) epilepsy with febrile seizures plus?

2009 ◽  
Vol 31 (5) ◽  
pp. 394-400 ◽  
Author(s):  
Ingrid E. Scheffer ◽  
Yue-Hua Zhang ◽  
Floor E. Jansen ◽  
Leanne Dibbens
Keyword(s):  
Febrile Seizures ◽  
Dravet Syndrome ◽  
Generalized Epilepsy ◽  
Febrile Seizures Plus

scholarly journals Febrile temperatures unmask biophysical defects in Nav1.1 epilepsy mutations supportive of seizure initiation

2013 ◽  
Vol 142 (6) ◽  
pp. 641-653 ◽  
Author(s):  
Linda Volkers ◽  
Kristopher M. Kahlig ◽  
Joost H.G. Das ◽  
Marjan J.A. van Kempen ◽  
Dick Lindhout ◽  
...  
Keyword(s):  
Voltage Dependence ◽  
Febrile Seizures ◽  
Dravet Syndrome ◽  
Slow Inactivation ◽  
Loss Of Function ◽  
Peak Current Density ◽  
Delayed Recovery ◽  
Generalized Epilepsy ◽  
Use Dependency ◽  
Febrile Seizures Plus

Generalized epilepsy with febrile seizures plus (GEFS+) is an early onset febrile epileptic syndrome with therapeutic responsive (a)febrile seizures continuing later in life. Dravet syndrome (DS) or severe myoclonic epilepsy of infancy has a complex phenotype including febrile generalized or hemiclonic convulsions before the age of 1, followed by intractable myoclonic, complex partial, or absence seizures. Both diseases can result from mutations in the Nav1.1 sodium channel, and initially, seizures are typically triggered by fever. We previously characterized two Nav1.1 mutants—R859H (GEFS+) and R865G (DS)—at room temperature and reported a mixture of biophysical gating defects that could not easily predict the phenotype presentation as either GEFS+ or DS. In this study, we extend the characterization of Nav1.1 wild-type, R859H, and R865G channels to physiological (37°C) and febrile (40°C) temperatures. At physiological temperature, a variety of biophysical defects were detected in both mutants, including a hyperpolarized shift in the voltage dependence of activation and a delayed recovery from fast and slow inactivation. Interestingly, at 40°C we also detected additional gating defects for both R859H and R865G mutants. The GEFS+ mutant R859H showed a loss of function in the voltage dependence of inactivation and an increased channel use-dependency at 40°C with no reduction in peak current density. The DS mutant R865G exhibited reduced peak sodium currents, enhanced entry into slow inactivation, and increased use-dependency at 40°C. Our results suggest that fever-induced temperatures exacerbate the gating defects of R859H or R865G mutants and may predispose mutation carriers to febrile seizures.

scholarly journals SCN1A Mutation—Beyond Dravet Syndrome: A Systematic Review and Narrative Synthesis

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiangwei Ding ◽  
Xinxiao Li ◽  
Haiyan Tian ◽  
Lei Wang ◽  
Baorui Guo ◽  
...  
Keyword(s):  
Rett Syndrome ◽  
Gene Mutations ◽  
Febrile Seizures ◽  
Autism Spectrum ◽  
Epileptic Encephalopathy ◽  
West Syndrome ◽  
Dravet Syndrome ◽  
Scn1a Mutation ◽  
Febrile Seizures Plus ◽  
Doose Syndrome

Background:SCN1A is one of the most common epilepsy genes. About 80% of SCN1A gene mutations cause Dravet syndrome (DS), which is a severe and catastrophic epileptic encephalopathy. More than 1,800 mutations have been identified in SCN1A. Although it is known that SCN1A is the main cause of DS and genetic epilepsy with febrile seizures plus (GEFS+), there is a dearth of information on the other related diseases caused by mutations of SCN1A.Objective: The aim of this study is to systematically review the literature associated with SCN1A and other non-DS-related disorders.Methods: We searched PubMed and SCOPUS for all the published cases related to gene mutations of SCN1A until October 20, 2021. The results reported by each study were summarized narratively.Results: The PubMed and SCOPUS search yielded 2,889 items. A total of 453 studies published between 2005 and 2020 met the final inclusion criteria. Overall, 303 studies on DS, 93 on GEFS+, three on Doose syndrome, nine on the epilepsy of infancy with migrating focal seizures (EIMFS), six on the West syndrome, two on the Lennox–Gastaut syndrome (LGS), one on the Rett syndrome, seven on the nonsyndromic epileptic encephalopathy (NEE), 19 on hemiplegia migraine, six on autism spectrum disorder (ASD), two on nonepileptic SCN1A-related sudden deaths, and two on the arthrogryposis multiplex congenital were included.Conclusion: Aside from DS, SCN1A also causes other epileptic encephalopathies, such as GEFS+, Doose syndrome, EIMFS, West syndrome, LGS, Rett syndrome, and NEE. In addition to epilepsy, hemiplegic migraine, ASD, sudden death, and arthrogryposis multiplex congenital can also be caused by mutations of SCN1A.

scholarly journals Generalized Epilepsy with Febrile Seizures Plus (GEFS+): Clinical Spectrum in Seven Italian Families Unrelated to SCN1A, SCN1B, and GABRG2 Gene Mutations

Epilepsia ◽  
2004 ◽  
Vol 45 (2) ◽  
pp. 149-158 ◽  
Author(s):  
Paolo Bonanni ◽  
Michela Malcarne ◽  
Francesca Moro ◽  
Pierangelo Veggiotti ◽  
Daniela Buti ◽  
...  
Keyword(s):  
Gene Mutations ◽  
Febrile Seizures ◽  
Clinical Spectrum ◽  
Generalized Epilepsy ◽  
Febrile Seizures Plus

Genetic epilepsy with febrile seizures plus

Neurology ◽  
2017 ◽  
Vol 89 (12) ◽  
pp. 1210-1219 ◽  
Author(s):  
Yue-Hua Zhang ◽  
Rosemary Burgess ◽  
Jodie P. Malone ◽  
Georgie C. Glubb ◽  
Katherine L. Helbig ◽  
...  
Keyword(s):  
Genetic Data ◽  
Febrile Seizures ◽  
Original Description ◽  
Molecular Data ◽  
Genetic Determinants ◽  
Genetic Epilepsy ◽  
Phenotypic Spectrum ◽  
Clonic Seizures ◽  
Generalized Epilepsy ◽  
Febrile Seizures Plus

Objective:Following our original description of generalized epilepsy with febrile seizures plus (GEFS+) in 1997, we analyze the phenotypic spectrum in 409 affected individuals in 60 families (31 new families) and expand the GEFS+ spectrum.Methods:We performed detailed electroclinical phenotyping on all available affected family members. Genetic analysis of known GEFS+ genes was carried out where possible. We compared our phenotypic and genetic data to those published in the literature over the last 19 years.Results:We identified new phenotypes within the GEFS+ spectrum: focal seizures without preceding febrile seizures (16/409 [4%]), classic genetic generalized epilepsies (22/409 [5%]), and afebrile generalized tonic-clonic seizures (9/409 [2%]). Febrile seizures remains the most frequent phenotype in GEFS+ (178/409 [44%]), followed by febrile seizures plus (111/409 [27%]). One third (50/163 [31%]) of GEFS+ families tested have a pathogenic variant in a known GEFS+ gene.Conclusion:As 37/409 (9%) affected individuals have focal epilepsies, we suggest that GEFS+ be renamed genetic epilepsy with febrile seizures plus rather than generalized epilepsy with febrile seizures plus. The phenotypic overlap between GEFS+ and the classic generalized epilepsies is considerably greater than first thought. The clinical and molecular data suggest that the 2 major groups of generalized epilepsies share genetic determinants.

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